Open AccessHIF Activation and VEGF Overexpression are Coupled with ZO‐1 Up‐phosphorylation in the Brain of Dystrophic MDX Mouse
Author(s) -
Nico Beatrice,
Mangieri Domenica,
Crivellato Enrico,
Longo Vito,
De Giorgis Michela,
Capobianco Carmen,
Corsi Patrizia,
Benagiano Vincenzo,
Roncali Luisa,
Ribatti Domenico
Publication year - 2007
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2007.00090.x
Subject(s) - vascular endothelial growth factor , angiogenesis , mdx mouse , phosphorylation , immunoprecipitation , biology , tight junction , immunohistochemistry , microbiology and biotechnology , kinase insert domain receptor , vascular endothelial growth factor a , duchenne muscular dystrophy , claudin , chemistry , cancer research , dystrophin , immunology , vegf receptors , antibody , genetics
In Duchenne muscular dystrophy (DMD) metabolic and structural alterations of the central nervous system are described. Here, we investigated in the brain of 10 mdx mice and in five control ones, the expression of hypoxia inducible factor‐1α (HIF‐1α) and we correlated it with the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor‐2 (VEGFR‐2) and of the endothelial tight junction proteins zonula occludens‐1 (ZO‐1) and claudin‐1. Results showed an activation of mRNA HIF‐1α by reverse transcription polymerase chain reaction (RT‐PCR) and a strong HIF1‐α labeling of perivascular glial cells and cortical neurons by immunohistochemistry, in mdx mouse. Moreover, overexpression of VEGF and VEGFR‐2, respectively, in neurons and in endothelial cells coupled with changes to endothelial ZO‐1 and claudin‐1 expression in the latter were detected by immunoblotting and immunohistochemistry, in the mdx brain. Furthermore, by immunoprecipitation, an up‐phosphorylation of ZO‐1 was demonstrated in mdx endothelial cells in parallel with the reduction in ZO‐1 protein content. These data suggest that the activation of HIF‐1α in the brain of dystrophic mice coupled with VEGF and VEGFR‐2 up‐regulation and ZO‐1 and claudin‐1 rearrangement might contribute to both blood–brain barrier opening and increased angiogenesis.